As disclosed in my above-identified applications, I have discovered that very large production of antibodies can be achieved by removing specific feedback regulatory antibodies by means of lymphoresis performed under special conditions in a patient or subject (e.g., an animal or human) with induced anatomical and physiological changes.
The subject is first given a specific antigen administration then, preferably, but not mandatorily, is splenectomized. A thoracic duct fistula is next performed. The central venous system pressure is then preferably raised so that it is above the atmospheric pressure of the thoracic duct. In this manner, substantialy all the lymph fluid is allowed to flow out of the thoracic duct from the fistula (through an indwelling catheter) for a prolonged period of time. The lymph is separated into cells and lymph fluid, which latter contains the antibody produced in response to the specific antigen admninistered. The cells are returned to the subject intravenously. The subject must be given replacement fluid, which can be of several kinds, but all lacking the specific antibody.
In accordance with the present invention, a subject which contains the specific antigen is chosen, e.g., a patient with cancer or a subject already immunized, or making antibodies to an endogenous or exogenous antigen. The fluid which leaves the patient via the thoracic duct fistula cannula consists of lymph generated by the patient, and saline, which is continuously infused into the cannula to dilute the lymph. The lymph is actually the only fluid lost from the patient, inasmuch as saline, which is constantly infused into the cannula leaves via the cannula.
Furthermore, as set forth below in detail, in accordance with the instant invention, the patient's venous pressure is precisely controlled to assure that the patient's total lymph production egresses from the cannula, thereby achieving the most efficient augmentation of antibody production by the patient, and total loss by the patient of the antibody produced.
Because of this lack of antibody, in the presence of antigen administration, or antigen content, it is found that the antibody production in the lymphoid tissue, and therefore its content in the lymph fluid, is enormous and ever-increases. The tremendous increase in antibody production is several orders of magnitude greater than other modes of antibody production, and therefore has very substantial utility in the fields of biology, chemistry and veterinary and clinical medicine.
However, conventional apparatus used for performing the steps of the foregoing method is costly, inefficient, and inter alia tends to foster the generation of bacterial growth.
Accordingly I have invented apparatus having general utility in biochemical research, and particular applicability in the performance of my method for augmenting the production of antibodies.
Furthermore, my invention of this apparatus made possible novel improvements in my method for agumenting antibody production, and as well led to my discovery of novel methods for the treatment of cancer, for continuous mass in vitro suspension culture of mammalian and non-mammalian cells and to my discovery of novel methods for culture treatment in order to develop vaccines.